He married Mary, sister of Henry Stafford, 5th Baron Stafford by a licence granted 11 Oct 1637. The Staffords were Catholics and the marriage was conducted by a Catholic priest, to the embarrassment of William's father. Following the forced surrender of the barony by Roger Stafford, 6th Baron Stafford, the Howard family secured the title for William, with them being created Baron and Baroness Stafford on 12 Sept 1640. Two months later, William was created Viscount Stafford.

Stafford and family left England in Aug 1641, moving to Antwerp; his parents had also left England and were in the same area. He was allowed by Parliament to return to England with Mary in 1646 and 1647, however in 1649 his estates were sequestered and compounded for recusancy and royalism. At his trial in 1680, he claimed he performed duties for King Charles I during this time, travelling between England and the Low Countries, plus visiting Rome, the Palatinate and Heidelberg; in the latter he was imprisoned for a year, allegedly for immorality. He was also imprisoned in 1656 in the Netherlands, for his father's debts. There were many quarrels over the Howard inheritance, especially between William and his elder brother's family, who had pursued a series of suit against his mother and him for additional money[2]

He returned to England with the Restoration in 1660 and was restored to his estates. He was never really prominent in political affairs nor amongst Catholics, although he did promote the removal of the anti-Catholic penal laws with King Charles II and James, Duke of York. He was also a member of the Royal Society from 1665, becoming a council member in 1672[1].

In 1678, he was implicated by Titus Oates in the Popish Plot fabricated by anti-Catholics and was sent to the Tower of London on 31 October 1678, along with four other Catholic peers. They were due to be put on trial in early 1679, but Charles prorogued Parliament and it was delayed. Scepticism of the plot grew and it was thought the imprisoned peers may have been released, but anti-Catholic feelings grew again in 1680 and Stafford was put on trial in November for impeachment. Evidence against Stafford was from Oates, who said he had seen a document from the Pope naming Stafford as a conspirator and from Stephen Dugdale, who testified that Stafford had tried to get him to kill the King. A third witness, Edward Tuberville said he had also visited Stafford in Paris and had also been asked to kill Charles. Stafford was denied counsel and forced to conduct his own defense,[6]. bringing forward witnesses to counter the evidence of his accusers. One such witness could have been Richard Gerard of Hilderstone who had come to London to testify, but was instead imprisoned on the word of Stephen Dugdale, and died in jail before the trial.[7]. The defence was not enough and Stafford was convicted by a majority of 55 to 31 and sentenced to the punishment of traitors, which was commuted to beheading. Stafford was executed on Tower Hill on 29 Dec 1680[1].

Stafford was attainted and the family lost the title; the title of Baron Stafford was returned to line in 1824 with the attainder being reversed but the title of Viscount was extinct as there were no male heirs. Mary Stafford had her title returned with the accession of James II and she was created Countess of Stafford on 5 Oct 1688, at the same time her son was created Earl of Stafford.

^ 7 Howell's State Trials, 1293, 1339 (House of Lords, Dec. 1, 1680)(he could not have counsel with him while evidence being presented against him). This very detailed transcript of the proceedings is available from Google books.